Globin biosynthesis in sickle cell, Hb SC, and Hb C diseases

The wide range of globin synthesis ratios reported in patients with sickle cell disease casts doubt on whether the presence of genes for α- or β-thalassemia in combination with Hb S can be detected by globin synthesis studies. We have studied globin synthesis in 20 patients with Hb SS who had a mean β s /α ratio of 1.05±0.04, similar to that of 28 control children. In nine of these patients the percentage of newly synthesized radioactive α-chains in dimer or monomer forms was 16.3%±1.3, also similar to the control subjects. The remainder of α-chain was in hemoglobin tetramer. In nine patients with Hb SC, the (non-α)/α ratio was 0.97±0.04, and the free α-chain pool radioactivity in four patients was 14.1%±4.2. In three patients with Hb CC, β c /α ratios were 0.99, 1.07, and 1.10. These results indicate that globin synthesis ratios and α-chain radioactivity in the free α-chain pool of peripheral blood of patients with Hb SS, Hb SC, and Hb CC have narrow ranges, close to those of nonthalassemic controls. The data provide a basis for detecting syndromes with Hb S or Hb C associated with α- or β-thalassemia. This precise differentiation is important for clinical studies of severity in sickle cell disease and for genetic counseling.